Question

Show how the following ketones might be synthesized by using the acetoacetic ester synthesis.

Short answer

(a)

(b)

(c)

Step-by-step solution

Step 1: Acetoacetic ester synthesis

In the Acetoacetic ester synthesis reaction, acetoacetic ester was treated with several reagents that converted it into the desired ketone.

In this reaction number of reagents are used in various steps to form the desired product:

• In the first step a baseis used to abstract the acidic proton to form an enolate. Example of base are NaOEt,${\text{NaNH}}_{\text{2}}$, etc
• In the second step, alkyl halide or aryl halide is added to give the desired alkyl or aryl acetoacetic ester, e.g., methylbromide, ethyl bromide, etc
• In the third step, hydrolysistakes place in the presence of aq KOH or ${\text{NaNH}}_{\text{2}}$
• In the last step, decarboxylation occurs due to heating $\left(\mathbf{\Delta }\right)$

 Synthesis of 4-phenylbutan-2-one

Ethoxide ion completely deprotonates acetoacetic ester ethyl 3-oxobutanoate.

The resulting enolate is alkylated by an aryl halide benzyl bromide to give an

alkylacetoacetic ester ethyl 2-benzyl-3-oxobutanoate. The alkylacetoacetic ester formed undergoes hydrolysis and decarboxylation to give the final desired product 4-phenylbutan-2-one.

Synthesis of 4-phenylbutan-2-one

 Synthesis of 4-phenylbutan-2-one

Ethoxide ion completely deprotonates acetoacetic ester ethyl 3-oxobutanoate.

The resulting enolate is alkylated by an akyl halide 1,4 dibromo butane to give an

alkylacetoacetic ester ethyl 1-acetylcyclopentanecarboxylate. The cyclic acetoacetic ester formed undergoes hydrolysis and decarboxylation to form the final desired product 1-cyclopentylethanone.

Synthesis of 1-cyclopentylethanone

 Synthesis of 4-phenylbutan-2-one 

Ethoxide ion completely deprotonates acetoacetic ester ethyl 3-oxobutanoate.

The resulting enolate is alkylated by an aryl halide benzyl bromide to give an

alkylacetoacetic ester ethyl 2-benzyl-3-oxobutanoate which on reacting with sodium ethoxide base and 3-bromopropene forms ethyl 2-acetyl-2-benzylpent-4-enoate which on hydrolysis and decarboxylation form the desired product 3-benzylhex-5-en-2-one.

Synthesis of 3-benzylhex-5-en-2-one